Healthy VolunteersPhase 1/2NCT00351416
Letrozole Treatment in Normal and GnRH Deficient Women
A Phase 1/2 study testing Letrozole and NAL-GLU GnRH antagonist in people with Healthy Volunteers, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Letrozole and NAL-GLU GnRH antagonist
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2004to 29 Jun 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy Normal Subjects will meet the following criteria:
- 18 to 35 years of age
- good general health
- on no medications including any hormonal drug products for at least 3 months before the study
- regular menstrual cycles every 25-35 days with ovulation documented by a luteal phase progesterone > 3 ng/ml
- no evidence of androgen excess
Show all 10Show fewer
- normal TSH, prolactin and hemoglobin
- use of double-barrier contraception, permanent sterilization or abstinence during the cycle of study.
- Negative pregnancy test (serum) at the beginning of each cycle of study
- Normal Liver Function Test
Who cannot join
- History of liver and/or kidney disease
- Substance or alcohol abuse
- Hormone dependent neoplasia including breast cancer
- Women who are trying to become pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Reproductive Endocrine Unit, Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. The NAL-GLU GnRH antagonist is a drug that temporarily blocks the action of GnRH. GnRH is a hormone that the body makes that stimulates other hormones that then control the function of the ovary.
The purpose is to study the effects of the administration of letrozole in women with GnRH deficiency at the same time that they receive gonadotropin-releasing hormone (GnRH). In addition, administration of letrozole and NAL-GLU GnRH antagonist in healthy women with normal menstrual cycles will be done to evaluate the role of estrogen in the control of the hormone FSH, or Follicle Stimulating Hormone, in the female reproductive cycle. A better understanding of FSH control may help in the development of new treatments for women with difficulty conceiving.
Read the detailed description
The negative feedback control of FSH is crucial for the precise regulation of follicular development in the female. An important component of this feedback is exerted by estrogen. Letrozole will be used to block aromatase and therefore estradiol production in normal and GnRH deficient females. These studies will dissect the relative roles of estradiol and inhibin on FSH secretion at the pituitary and hypothalamus.
The aromatase inhibitors block aromatization of androgens to estrogens, allowing us to examine the relative contribution of estradiol and the inhibins to FSH regulation. The use of a submaximal dose of a GnRH antagonist will allow us to estimate the overall amount of GnRH secreted (hypothalamic contribution) with and without aromatase inhibition.
A more thorough understanding of estrogen and inhibin feedback on FSH will improve our understanding of the failure of follicle development in subsets of patients with infertility, such as polycystic ovary syndrome, in which FSH levels are normal but follicles fail to develop. Study of FSH control will also help us understand the failure of negative feedback on FSH, which can result in multiple follicular development and multiple gestation and its associated costs and risks. Thus, these studies may afford new therapeutic options for conception in infertile patients while simultaneously providing new methods to avoid the risks of multiple gestations.
- Conditions
- Healthy Volunteers
- Being tested
- Letrozole, NAL-GLU GnRH antagonist
- Keywords
- GnRH deficiency, GnRH antagonist, Letrozole, GnRH, FSH, LH, Inhibins
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Also called aromatase inhibitor, Femara
Letrozole 20 mg orally one time
NAL-GLU GnRH antagonistDrug
Also called GnRH antagonist
5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Aromatase inhibitor EFP | Experimental | Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and
Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Receives: Drug: Letrozole; Drug: NAL-GLU GnRH antagonist |
| Aromatase inhibitor LFP | Experimental | Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2.
Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Receives: Drug: Letrozole; Drug: NAL-GLU GnRH antagonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
FSH Level
Difference in FSH peak following letrozole administration compared with control cycle
Measured: EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2006 (estimated)
- Study start21 Jan 2004
- Primary completion29 Jun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is a physiologic study designed to investigate the relative roles of estradiol and inhibin A or inhibin B in the control of FSH secretion during normal menstrual cycles using an aromatase inhibitor. Subjects serve as their own control with no intervention in cycle 1 and letrozole administration in cycle 2. Subjects are studied in the early follicular phase or the late follicular phase.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Janet E. Hall, MD, Massachusetts General Hospital
- Investigators
- Janet E Hall, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00351416
- Sponsor's protocol ID
- 2003-P-001895
- Other IDs
- Sundry Department Fund
- Status last verified
- Jun 2017
- First submitted
- 10 Jul 2006
- Last updated
- 27 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Once published, de-identified individual level data will be shared upon request to the PI.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letrozole Treatment in Normal and GnRH Deficient Women
- ClinicalTrials.gov ID
- NCT00351416
- Acronym / sponsor ID
- 2003-P-001895
- Conditions
- Healthy Volunteers
- Keywords
- GnRH deficiency, GnRH antagonist, Letrozole, GnRH, FSH, LH, Inhibins
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 21 Jan 2004 (actual)
- Primary completion
- 29 Jun 2009 (actual)
- First posted
- 12 Jul 2006 (estimated)
- Results
- Posted 27 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. The NAL-GLU GnRH antagonist is a drug that temporarily blocks the action of GnRH. GnRH is a hormone that the body makes that stimulates other hormones that then control the function of the ovary.
The purpose is to study the effects of the administration of letrozole in women with GnRH deficiency at the same time that they receive gonadotropin-releasing hormone (GnRH). In addition, administration of letrozole and NAL-GLU GnRH antagonist in healthy women with normal menstrual cycles will be done to evaluate the role of estrogen in the control of the hormone FSH, or Follicle Stimulating Hormone, in the female reproductive cycle. A better understanding of FSH control may help in the development of new treatments for women with difficulty conceiving.
Detailed description
The negative feedback control of FSH is crucial for the precise regulation of follicular development in the female. An important component of this feedback is exerted by estrogen. Letrozole will be used to block aromatase and therefore estradiol production in normal and GnRH deficient females. These studies will dissect the relative roles of estradiol and inhibin on FSH secretion at the pituitary and hypothalamus.
The aromatase inhibitors block aromatization of androgens to estrogens, allowing us to examine the relative contribution of estradiol and the inhibins to FSH regulation. The use of a submaximal dose of a GnRH antagonist will allow us to estimate the overall amount of GnRH secreted (hypothalamic contribution) with and without aromatase inhibition.
A more thorough understanding of estrogen and inhibin feedback on FSH will improve our understanding of the failure of follicle development in subsets of patients with infertility, such as polycystic ovary syndrome, in which FSH levels are normal but follicles fail to develop. Study of FSH control will also help us understand the failure of negative feedback on FSH, which can result in multiple follicular development and multiple gestation and its associated costs and risks. Thus, these studies may afford new therapeutic options for conception in infertile patients while simultaneously providing new methods to avoid the risks of multiple gestations.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a physiologic study designed to investigate the relative roles of estradiol and inhibin A or inhibin B in the control of FSH secretion during normal menstrual cycles using an aromatase inhibitor. Subjects serve as their own control with no intervention in cycle 1 and letrozole administration in cycle 2. Subjects are studied in the early follicular phase or the late follicular phase.
| Arm | Type | Receives |
|---|---|---|
| Aromatase inhibitor EFP | Experimental | Drug: Letrozole, Drug: NAL-GLU GnRH antagonistLetrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
| Aromatase inhibitor LFP | Experimental | Drug: Letrozole, Drug: NAL-GLU GnRH antagonistLetrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 18 to 35 years of age
- good general health
- on no medications including any hormonal drug products for at least 3 months before the study
- regular menstrual cycles every 25-35 days with ovulation documented by a luteal phase progesterone > 3 ng/ml
- no evidence of androgen excess
Key exclusion criteria (4 listed)
- History of liver and/or kidney disease
- Substance or alcohol abuse
- Hormone dependent neoplasia including breast cancer
- Women who are trying to become pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozoleAlso: aromatase inhibitor, FemaraLetrozole 20 mg orally one time | Drug | Aromatase inhibitor EFP, Aromatase inhibitor LFP |
| NAL-GLU GnRH antagonistAlso: GnRH antagonist5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously | Drug | Aromatase inhibitor EFP, Aromatase inhibitor LFP |
Primary outcome
FSH Level
Time frame: EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm
Difference in FSH peak following letrozole administration compared with control cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Once published, de-identified individual level data will be shared upon request to the PI.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet E Hall, M.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Letrozole and NAL-GLU GnRH antagonist in people with Healthy Volunteers, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FSH Level (time frame: EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2017.